Purpose:
The purpose of this research is to check if eye movements can be used as biomarkers to quantify the appearance and progress of the disease even presymptomatically.

Methods:
Spinocerebellar Ataxia Type 3 (SCA-3), also known as Machado-Joseph Disease (MJD), is an autosomal dominant neurodegenerative disorder for which genetic testing can reveal those at risk for developing the disease. The time at which a given individual begins to show symptoms is highly variable, with clinical diagnosis dependent on motor symptoms. Quantitative measures that would identify premanifest gene carriers (PMGC) at the threshold of clinical diagnosis would be extremely valuable in early diagnosis, tracking disease progression and assessing treatment. The head impulse test (HIT) assesses vestibular function with brisk, passive rotations of the head in the plane of parallel semicircular canal pairs and it may be useful as a means of detecting early stages of the disease. Using the magnetic search coil technique we recorded monocular eye movements and head movements of 4 subjects at risk for developing SCA-3. Three of the patients have been genetically tested and found to have expanded “CAG” repeats in the ATXN3 gene, i.e. they will develop the disease at some point. The fourth is a sibling of a symptomatic MJD patient who has heretofore declined genetic testing. In addition, we recorded eye movements of 10 symptomatic SCA-3 patients. Among the eye movement paradigms used were saccades, smooth pursuit, and the head impulse test.

Results:
We found that the four presymptomatic subjects all have a reduction in the gain of the VOR as measured using the head impulse test. Nonetheless, we did not find any deficit in either their saccades or smooth pursuit. In contrast, all of the symptomatic patients had saccadic and smooth pursuit deficits, in addition to impaired VOR.

Conclusions:
Individuals at risk for developing MJD can be asymptomatic for years before receiving formal diagnosis. Our preliminary results suggest that the head impulse test (HIT) may provide biomarkers useful in tracking phenotypic change in such individuals.